Method for producing a bone material enriched with bone growth factors

ABSTRACT

The aim of the invention is to produce a bone material which is enriched with bone growth factors and whose bone growth factors are released in a delayed manner after surgically applied in the body. To this end, the invention provides a method according to which the bone material is loaded with a bone growth factor or with a mixture of bone growth factors and is then coated with a reabsorbable substance.

[0001] So-called BMPs (bone morphogenetic proteins) play a decisive role in the growth of human or animal bones. Expedient methods have been developed to harvest these growth factors in which bone material was demineralized and growth factors were enriched in the demineralized bone material. The bone material enriched with growth factors is used in particular in surgery to promote bone growth at defective areas and to accelerate the healing process of the bone.

[0002] Methods are furthermore known of separating and harvesting different growth factors from bones. In deviation from this, preparative amounts of bone growth factors can be gained in a genetic engineering manner.

[0003] In previously practiced methods it is disadvantageous that, when bone material enriched with bone growth factors is used in surgery, the bone growth factors are prematurely washed out so that the accelerated bone growth cannot be maintained over the total healing process of the bone.

[0004] The underlying object of the invention is to provide a method with which a bone material enriched with bone growth factors can be manufactured with an improved release rate.

[0005] This object is satisfied in accordance with the invention by a method having the features of claim 1.

[0006] The invention is based on the recognition that the surface and/or the interior of bone material can also be sheathed by a resorbable material with the aid of a suitable method, with the sheathing of a bone material enriched or charged with bone growth factors then bringing about the intended delayed release of the bone growth factors. In this manner, in a surgical use of the bone material as a transplant, the bone growth factors can be released continuously over a longer period and over the total healing process of a bone, with the length and the speed of the release being dependent on the properties of the sheathing. A control of the agent release is possible, for example, via the thickness and the material composition of the sheathing.

[0007] Advantageous embodiments of the invention are described in the description and the dependent claims.

[0008] A solution or suspension of the bone growth factors is advantageously sprayed or trickled onto the surface of a suitable bone material, for example bovine spongiosa, which has been freed of bone marrow in a conventional manner. It is furthermore possible to immerse the bone material into the solution so that the solution is sucked in by the surface of the bone material. In this connection, the bone growth factors are predominantly, but not exclusively, deposited in a surface region of the bone material, with the bone material enriched with bone growth factors being sheathed subsequent to this treatment.

[0009] To enrich the bone growth factors increasingly also at the interior of the bone material, in a further development a vacuum is applied during the spraying on, trickling on or sucking in of the solution or suspension. Air, which otherwise prevents the entrance of solvent or suspension, is sucked off from the interior of the bone material by the vacuum applied.

[0010] In a further variant, the charged bone material, which is thus enriched with bone growth factors, is embedded in pre-fabricated capsules, hollows or pockets of resorbable material for sheathing.

[0011] In accordance with a further embodiment, the bone growth factors can be homogeneously distributed in a solution or suspension of the resorbable material. This solution or suspension can subsequently be sprayed or trickled onto the surface of the bone material. It is furthermore possible to immerse the bone material into the said solution or suspension. In the above-described process steps, the solution or suspension essentially only penetrates into the surface region of the bone material. The treatment of the bone material with bone growth factors, which takes place at the same time, and its sheathing with resorbable material, therefore substantially remains limited to the surface, with both the bone growth factors and the bone material being sheathed by the resorbable material in this manner.

[0012] In a preferred embodiment of the method in accordance with the invention, a vacuum is applied during the trickling on, spraying on or sucking in of the solution or suspension containing the resorbable solution or suspension so that the interior of the bone material is also increasingly enriched and sheathed with sheathed bone growth factors.

[0013] Collagen, which is available in a dissolved or dispersed manner or as a gel, is advantageously used as the resorbable material. Further examples of resorbable materials are gelatin or oxycellulose. The bone material can be used in the form of blocks, chips or powder. In accordance with the invention, it can be available in a usual mineral/matrix composition. Expediently, however, bone material is used in the method in accordance with the invention which is fully or partly demineralized. The bone material used can be both of animal and of human origin.

[0014] In a further advantageous variant, the bone growth factor(s) are homogeneously distributed in a solution or suspension of the resorbable material. Subsequently, bone material is introduced into this solution in the form of powder or chips and the intermediate product thus obtained dried, preferably freeze dried, to form a sponge-like body. A product which is extremely helpful for surgery can hereby be obtained.

[0015] In an expedient further development, the bone material is also charged with at least one anti-biotic. The charging can take place in any desired manner, for example by the addition of the antibiotic to the solution or suspension of the resorbable material or by trickling the antibiotic onto the bone material. The charged bone material sheathed with resorbable material is preferably freeze dried or dried by heat.

[0016] In a further expedient further development, the charged and sheathed bone material is produced in a germ-free manner or is sterilized after the drying.

[0017] Two examples of the method in accordance with the invention will be described in the following:

EXAMPLE 1

[0018] 100 ml of an 0.5% collagen solution produced in a known manner are mixed with 100 mg rhBMH-2 in a vessel and carefully stirred until homogenous. A bovine spongiosa bone with the dimensions 3×3×2 cm³ is subsequently immersed into the collagen/BMP solution and left in the solution under vacuum for 10 minutes. The spongiosa block treated in this manner is subsequently removed from the vessel, put into a tub and frozen and dried in steps in a freeze drying unit. Finally, the spongiosa block enriched with BMP and sheathed with collagen is sterilized in a suitable manner.

[0019] The spongiosa block produced in accordance with the method described contains BMP enclosed in collagen so that a premature washing out in a surgical application as a transplant is prevented. A delayed release of BMP takes place in accordance with the collagen depletion.

[0020] An accelerated new formation of bone at a defective area takes place due to the inductive effect of the BMPs enriched in the transplant.

EXAMPLE 2

[0021] 100 ml of a 1.0% collagen solution produced in a known manner are mixed with 100 mg rhBMP-2 in a vessel and carefully stirred until homogeneous. The BMP/collagen solution is subsequently poured into a metal tub and bone material is added, for example in the form of chips of bovine bone of a diameter of approximately 8 millimeters and a vacuum is applied for the better penetration of the chips with solution. The tub with contents is frozen and dried in steps in a freeze drying plant. Finally, the resulting product is sterilized in a suitable manner. 

1. A method of manufacturing a bone material enriched with bone growth factors, wherein the surface and/or the interior of the bone material is charged with at least one bone growth factor (BMP) and is sheathed with a resorbable material, wherein the bone material is initially charged by spraying on, trickling on or sucking in of a solution or suspension of the bone growth factor or by immersing into a solution or suspension of the bone growth factor and the bone material treated in this manner is subsequently sheathed.
 2. A method in accordance with claim 1, characterized in that the interior of the bone material is also charged with bone growth factors by application of a vacuum during the spraying on, trickling on or sucking in of the solution or suspension.
 3. A method in accordance with claim 1 or claim 2, characterized in that the charged bone material is embedded in pre-fabricated capsules, depressions or pockets of a resorbable material for the sheathing.
 4. A method in accordance with claim 1 or claim 2, characterized in that the sheathing of the surface and/or of the interior of the bone material takes place by spraying on, trickling on or sucking in of a solution or suspension of the resorbable material, preferably under vacuum.
 5. A method in accordance with claim 1, characterized in that the bone growth factor(s) are homogeneously distributed in a solution or suspension of the resorbable material and the surface and/or the interior of the bone material is subsequently charged with bone growth factors by spraying on or trickling on or sucking in of this solution or suspension and is sheathed with resorbable material.
 6. A method in accordance with any one of the preceding claims, characterized in that collagen is used as the resorbable material in the form of a solution, of a suspension, as a gel or gelatin, polyglycol acid, polylactic acid, oxycellulose or fabric adhesive, for example fibrin adhesive or acrylic adhesive.
 7. A method in accordance with any one of the preceding claims, characterized in that bone material is used in the form of blocks, chips or powder.
 8. A method in accordance with any one of the preceding claims, characterized in that the bone growth factor(s) are homogeneously distributed in a solution or suspension of the resorbable material, bone material is subsequently introduced into this solution in the form of powder or chips and the intermediate product obtained in this manner is subsequently dried, preferably freeze dried, to form a sponge-like body.
 9. A method in accordance with any one of the preceding claims, characterized in that fully or partly demineralized bone material is used.
 10. A method in accordance with any one of the preceding claims, characterized in that the bone material is charged with at least one antibiotic.
 11. A method in accordance with any one of the preceding claims, characterized in that the charged bone material is freeze dried.
 12. A bone material manufactured by a method in accordance with at least one of the preceding claims.
 13. Use of a bone material in accordance with claim 12 as a surgical transplant. 